Activity-Based Nanosensors of Lung Cancer

Technology

This technology is based on inhalable nanosensors consisting of a scaffold linked to one or more protease-cleavable substrates. Each substrate is conjugated to a small detectable marker via a cleavable linker. In lung cancer, dysregulated protease activity plays a direct role in all hallmarks of the disease, and several proteases are well-established as biomarkers for detection. Additionally, in lung infections, the lung microenvironment is disrupted by both immune proteases and pathogen-derived enzymes, which creates distinctive protease activity patterns. When a nanosensor encounters a lung disease-associated protease, the protease cleaves its substrate at a specific sequence, releasing the detectable marker from the scaffold. The marker is small enough to enter circulation and accumulates in the urine, which is then analyzed using a simple capture assay, such as a paper test strip.  

Problem Addressed

Early detection of lung diseases, including lung cancer and severe lung infections,  remains a major challenge. Lung cancer screenings for earlier detection is particularly difficult, as most patients are diagnosed after their disease has reached a stage too advanced for curative treatment. The current gold standard for lung cancer screening, low-dose computed tomography, suffers from poor specificity, high false positive rates, and scalability issues due to significant personnel and equipment requirements. Similarly, timely and accurate diagnosis of lung infections, such as bacterial pneumonia, is critical for reducing morbidity and mortality. Current diagnostic approaches often rely on imaging, sputum cultures, or molecular tests, which can be slow, invasive, or lack sensitivity. Technologies such as gene expression-mediated classifiers and ctDNA profiling are limited in sensitivity for early-stage lung cancer, and alternative strategies, such as analysis of volatiles in exhaled breath, require further validation in malignant rather than benign pulmonary diseases. This technology addresses key challenges in lung cancer and infection detection by enabling improved sensitivity relative to existing methods, while providing a non-invasive, low-cost, and highly scalable approach.  

Advantages

• Highly sensitive detection of lung disease-associated protease activity, with improved sensitivity relative to existing diagnostics
• Non-invasive detection enabled by simple administration through inhalation
• Low cost and minimal equipment required, making it highly scalable
• Ability to screen for lung cancer at earlier stages than traditional approaches by targeting protease activity
• Potential for rapid classification and monitoring of lung infections, supporting timely and appropriate treatment decisions
• Demonstrated high accuracy in early-stage detection of lung tumors in preclinical mouse studies